Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic Gene Ontology annotation based on Rhea mapping
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Human IL4I1 is a secreted L-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation.
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IL4I1 has L-amino acid oxidase activity, primarily toward phenylalanine
"We showed that IL4I1 has l-amino acid oxidase activity, optimal at physiological pH and primarily directed toward phenylalanine."
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IL4I1 is secreted into extracellular medium
"Both proteins were secreted into the culture medium, and we observed the secretion of endogenous human IL4I1 (hIL4I1) protein in a mediastinal lymphoma B-cell line, MedB-1."
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IL4I1 inhibits T cell proliferation via H2O2 production
"hIL4I1 inhibited the proliferation of CD3-stimulated T lymphocytes with a similar effect on CD4(+) and CD8(+) T cells. In contrast, memory T cells were more strongly affected by hIL4I1 and its catabolite H(2)O(2) than naive T cells. hIL4I1 inhibitory effect was dependent on enzymatic activity and H(2)O(2) production"
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Expressed by mature dendritic cells and macrophages
"Immunohistochemical analysis of secondary lymphoid organs showed staining of germinal center macrophages and inflammatory myeloid cells. In vitro, functional enzyme was highest in mature dendritic cells (DCs), suggesting a role in antigen-presenting cell/T-lymphocyte cross-talk."
Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function.
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IL4I1 is present in human spermatozoa
"we demonstrate for the first time that human spermatozoa possess interleukin-induced gene 1 (IL4I1), an l-amino acid oxidase (LAAO) which is capable of generating ROS on exposure to aromatic amino acids in the presence of oxygen."
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Localized to acrosomal region and midpiece
"the enzyme was located in the acrosomal region and midpiece of these cells."
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Preferred substrates are phenylalanine and tryptophan
"The preferred substrates were found to be phenylalanine and tryptophan"
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May regulate capacitation and acrosomal exocytosis
"Stimulation of LAAO activity resulted in the induction of several hallmarks of capacitation including tyrosine phosphorylation of the sperm flagellum and concomitant activation of phospho-SRC expression. In addition, stimulation of LAAO resulted in an increase in the levels of acrosomal exocytosis in both the presence and absence of progesterone stimulation"
The immunosuppressive enzyme IL4I1 promotes FoxP3(+) regulatory T lymphocyte differentiation.
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IL4I1 promotes FoxP3+ Treg differentiation
"We show that IL4I1 stimulates the generation of Foxp3(+) regulatory T (Treg) cells in vitro from human and mouse T cells."
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Effect mediated through phenylalanine consumption and mTORC1 inhibition
"Analysis of Treg-cell induction under conditions of Phe deprivation and hydrogen peroxide addition suggests that Phe consumption by the enzyme participates in Treg-cell enrichment. In line with this hypothesis, IL4I1 inhibits mTORC1 signaling shortly after T-cell activation."
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IL4I1 limits Th1 and Th2 polarization
"Conversely, IL4I1 limits Th1 and Th2 polarization while modifying the Th17 phenotype, in particular, by inducing its own production."
Alterations of the immunosuppressive IL4I1 enzyme activity induced by naturally occurring SNP/mutations.
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IL4I1 also has weak activity against L-arginine
"we show that IL4I1 activity is not only directed against phenylalanine, as initially described, but also at a lower level against arginine."
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Natural SNPs can alter enzyme activity (N92D hyperactive, R102G hypomorphic)
"The N92D SNP leads to a hyperactive enzyme, while the R102G mutation is hypomorphic."
IL4-induced gene 1 is secreted at the immune synapse and modulates TCR activation independently of its enzymatic activity.
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IL4I1 is secreted at the immunological synapse
"Focal secretion of IL4I1 into the immune synaptic cleft and its binding to CD3+ lymphocytes could be important in IL4I1 immunosuppressive mechanism of action."
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Decreases TCR signaling events
"the presence of IL4I1 during T-cell activation decreases early signaling events downstream of TCR stimulation, resulting in global T-cell inhibition which is more pronounced when there is CD28 costimulation."
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Some effects independent of enzymatic activity
"Surprisingly, the enzymatic activity of IL4I1 is not involved."
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
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High-throughput Y2H interactome screen
"Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions."
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IL4I1 identified in network but not primary focus of study
"Interactome maps are valuable resources to elucidate protein function and disease mechanisms."
IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression.
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IL4I1 activates AHR through indole metabolites and kynurenic acid
"IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid."
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Suppresses anti-tumor immunity
"suppresses adaptive immunity, thereby enhancing the progression of chronic lymphocytic leukemia (CLL) in mice."
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Promotes tumor progression
"promotes cancer cell motility, and suppresses adaptive immunity, thereby enhancing the progression of chronic lymphocytic leukemia (CLL) in mice."
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Associates with poor prognosis in glioma
"It associates with reduced survival in glioma patients"
Endogenous Indole Pyruvate Pathway for Tryptophan Metabolism Mediated by IL4I1.
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IL4I1 catalyzes Trp to IAA and IAld production
"we constructed an IL4I1-overexpressed 293T cell line and found that IL4I1 can catalyze Trp to produce indole-3-acetic acid (IAA) and indole-3-carboxaldehyde (IAld)."
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Establishes endogenous indole pyruvate pathway in host cells
"Our results demonstrate the existence of the indole pyruvate pathway in host cells with IL4I1 as the key enzyme."
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Products activate AHR through CYP1A1 expression
"both IAA and IAld are accumulated in dendritic cells (DCs) and can stimulate the expression of CYP1A1."
IL4I1:FAD oxidises L-Phe to kPPV
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Reactome pathway annotation for phenylalanine metabolism
"Extracellular L-amino-acid oxidase (IL4I1) catalyzes the reaction of phenylalanine, water, and molecular oxygen to form keto-phenylpyruvate, ammonia, and hydrogen peroxide. IL4I1, inferred to form a complex with FAD, has L-amino acid oxidase activity and with a strong preference for phenylalanine."
Deep research on IL4I1 function